Tretinoin, also known as all-trans retinoic acid (ATRA), is medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream or ointment. For leukemia, it is taken by mouth for up to three months.
|Pronunciation||See pronunciation note|
|Trade names||Vesanoid, Avita, Renova, Retin-a, others|
|topical, by mouth|
|Protein binding||> 95%|
|Elimination half-life||0.5-2 hours|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||300.4412 g/mol g·mol−1|
|3D model (JSmol)|
|Melting point||180 °C (356 °F)|
Common side effects when used by mouth include shortness of breath, headache, numbness, depression, skin dryness, itchiness, hair loss, vomiting, muscle pains, and vision changes. Other severe side effects include high white blood cell counts and blood clots. When used as a cream, side effects include skin redness, peeling, and sun sensitivity. Use during pregnancy is contraindicated due to the risk of birth defects. It is in the retinoid family of medications.
Tretinoin was patented in 1957 and approved for medical use in 1962. It is on the World Health Organization's List of Essential Medicines, which lists the safest and most effective medicines needed in a health system. Tretinoin is available as a generic medication. In the United Kingdom the cream together with erythromycin costs the NHS about £7.05 per 25 mL while the pills are £1.61 per 10 mg. In 2016 it was the 297th most prescribed medication in the United States with more than a million prescriptions.
People using the topical form should not also use any cream or lotion that has a strong drying effect, contains alcohol, astringents, spices, lime, sulfur, resorcinol, or aspirin, as these may interact with tretinoin or exacerbate its side effects.
Tretinoin is used to induce remission in people with acute promyelocytic leukemia who have a mutation (the t(15;17) translocation 160 and/or the presence of the PML/RARα gene) and who don't respond to anthracyclines or can't take that class of drug. It is not used for maintenance therapy.
By mouth, this drug is pregnancy category D and should not be used by pregnant women as it may harm the fetus.
Topical tretinoin is only for use on skin and it should not be applied to eyes or mucosal tissues. Common side effects include skin irritation, redness, swelling, and blistering.
There are many significant side effects from this drug that include malaise (66%), shivering (63%), hemorrhage (60%), infections (58%), peripheral edema (52%), pain (37%), chest discomfort (32%), edema (29%), disseminated intravascular coagulation (26%), weight increase (23%), injection site reactions (17%), anorexia (17%), weight decrease (17%), and myalgia (14%).
Respiratory side effects usually signify retinoic acid syndrome, and include upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), and expiratory wheezing (14%), and many others at less than 10%.
Around 23% of people taking the drug have reported earache or a feeling of fullness in their ears.
Gastrointestinal disorders include bleeding (34%), abdominal pain (31%), diarrhea (23%), constipation (17%), dyspepsia (14%), and swollen belly (11%) and many others at less than 10%.
In the cardiovascular system, side effects include arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%), phlebitis (11%), and cardiac failure (6%) and for 3% of patients: cardiac arrest, myocardial infarction, enlarged heart, heart murmur, ischemia, stroke, myocarditis, pericarditis, pulmonary hypertension, secondary cardiomyopathy.
Mechanism of actionEdit
For its use in cancer, its mechanism of action is unknown, but on a cellular level, laboratory test show that tretinoin forces APL cells to differentiate and stops them from proliferating; in people there is evidence that it forces the primary cancerous promyelocytes to differentiate into their final form, allowing normal cells to take over the bone marrow. Recent study shows that ATRA inhibits and degrades active PIN1.
For its use in acne, the mechanism is unknown, but again on a cellular level there is evidence that it decreases the ability of epithelial cells in hair follicles to stick together, leading to fewer blackheads; it also seems to make the epithelial cells divide faster, causing the blackheads to be pushed out.
Tretinoin is synthesized from Beta-carotene. The Beta-carotene is firstly cleaved into Beta-carotene 15-15'-monooxygenase through site 1 double bond oxidized to epoxide. The epoxide is attacked by water to form diol in site 1. NADH, as a reduction agent, reduce the alcohol group to aldehydes.
Tretinoin was co-developed for its use in acne by James Fulton and Albert Kligman when they were at University of Pennsylvania in the late 1960s. The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.
The origin of the name tretinoin is uncertain, although several sources agree (one with probability, one with asserted certainty) that it probably comes from trans- + retinoic [acid] + -in, which is plausible given that tretinoin is the all-trans isomer of retinoic acid. The name isotretinoin is the same root tretinoin plus the prefix iso-. Regarding pronunciation, the following variants apply equally to both tretinoin and isotretinoin. Given that retinoic is pronounced //, it is natural that // is a commonly heard pronunciation. Dictionary transcriptions also include // (tri-TIN-oh-in) and //.
- "Tretinoin". The American Society of Health-System Pharmacists. Archived from the original on 30 November 2016. Retrieved 8 December 2016.
- Tivnan A (2016). Resistance to Targeted Therapies Against Adult Brain Cancers. Springer. p. 123. ISBN 9783319465050. Archived from the original on 2017-11-05.
- British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 627, 821–822. ISBN 9780857111562.
- Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 476. ISBN 9783527607495. Archived from the original on 2017-11-05.
- "World Health Organization model list of essential medicines: 21st list 2019". 2019. hdl:10665/325771. Cite journal requires
- "Tretinoin topical". The American Society of Health-System Pharmacists. Archived from the original on 16 May 2016. Retrieved 8 December 2016.
- "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
- Topical Cream Gel Liquid Label Archived 2011-12-29 at the Wayback Machine
- Oral Label Archived 2016-05-08 at the Wayback Machine
- Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, et al. (August 1988). "Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia" (PDF). Blood. 72 (2): 567–72. PMID 3165295.
- Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L (November 1990). "All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results" (PDF). Blood. 76 (9): 1704–9. PMID 2224119.
- Wei S, Kozono S, Kats L, Nechama M, Li W, Guarnerio J, et al. (May 2015). "Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer". Nature Medicine. 21 (5): 457–66. doi:10.1038/nm.3839. PMC 4425616. PMID 25849135.
- Woggon W (2009). "Oxidative cleavage of carotenoids catalyzed by enzyme models and beta-carotene 15,15´-monooxygenase". Pure and Applied Chemistry. 74 (8): 1397–1408. doi:10.1351/pac200274081397. ISSN 1365-3075.
- Vivant Pharmaceuticals, LLC Press Release. July 10, 2013, Vivant Skin Care Co-founder James E. Fulton, MD, Loses Colon Cancer Battle
- Gellene D (22 February 2010). "Dr. Albert M. Kligman, Dermatologist, Dies at 93". The New York Times.}
- Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster.
- Oxford Dictionaries, Oxford Dictionaries Online, Oxford University Press, archived from the original on 2014-10-22.
- Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, archived from the original on 2015-09-25.
- Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
- Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
- Ralph M. Trüeb. The Difficult Hair Loss Patient: Guide to Successful Management of Alopecia and Related Conditions. Springer, 2015. ISBN 9783319197012 Pg. 95 Archived 2017-11-05 at the Wayback Machine
- Rogers NE, Avram MR (October 2008). "Medical treatments for male and female pattern hair loss". Journal of the American Academy of Dermatology. 59 (4): 547–66, quiz 567–8. doi:10.1016/j.jaad.2008.07.001. PMID 18793935.
- Arthur W. Perry (2007). Straight talk about cosmetic surgery. Yale University Press. p. 63. ISBN 978-0-300-12104-9.
- Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G (December 2006). "Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety". Clinical Interventions in Aging. 1 (4): 327–48. doi:10.2147/ciia.2006.1.4.327. PMC 2699641. PMID 18046911.
- Tretinoin AHFS Consumer Medication Information at PubMed Health